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The influence of exercise training on bone health in patients taking high doses of glucocorticoids

Grant number: 20/07860-9
Support Opportunities:Scholarships in Brazil - Doctorate (Direct)
Effective date (Start): September 01, 2020
Effective date (End): October 31, 2023
Field of knowledge:Biological Sciences - Physiology - Physiology of Organs and Systems
Acordo de Cooperação: CONFAP ; Newton Fund, with FAPESP as a partner institution in Brazil ; UK Academies
Principal Investigator:Eimear Bernadette Dolan
Grantee:Gabriel Perri Esteves
Host Institution: Faculdade de Medicina (FM). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:19/05616-6 - The bone response to exercise: a translational research program exploring clinical and mechanistic aspects, AP.JP

Abstract

Exercise is an important means to optimize bone accrual and maintenance throughout the lifespan and to manage or treat conditions that cause bone loss or weakening. Additionally, the use of distinct exercise types and intensities provides unique opportunities to investigate the bone response to various metabolic and mechanical signals, thus providing an in vivo model to study bone physiology. Despite the importance of exercise as a model to understand basic bone physiology, and as a strategy to enhance bone health, little is known about the pathways that mediate the bone response to exercise, nor of the factors that moderate this response. Thus, the ability to develop and administer targeted and effective therapeutic exercise programs is limited. The proposed research program sits at the crucial interface between basic and applied science, and addresses important knowledge gaps in this topic area. As recommended by the UK Medical Research Council (along with many other research bodies), the original investigations described herein will be preceded by a statistical meta-analysis of all available data on the bone metabolic response to exercise (Study 1). Onward progression of knowledge in this clinically essential area is impeded by an incomplete understanding of current data, and this is mainly due to large heterogeneity in study design and quality. The proposed rigorously designed meta-analysis will combine high-quality data using multi-level modelling based on Bayesian principles, and will ensure that the proposed research program is grounded in the most up-to-date and highest-quality evidence available. Central to the proposed research program is a clinical RCT (Study 2), which will investigate the independent and combined influences of exercise training and protein supplementation on bone in a group of patients prescribed high-dose glucocorticoid therapy (GCT). This group are highly susceptible to bone loss and fracture, but the potential of exercise to protect bone when delivered as an adjunctive therapy to GCT has never been examined. Within this study, we will investigate important clinical outcomes (including bone mass and micro-architecture, along with physical function). To provide additional scientific rigor, we will also use bone biopsies and bone biomarkers to glean more in-depth mechanistic insight into the clinical results obtained. This clinical trial will be complemented by a number of in vivo laboratory-based mechanistic studies, within which we will examine the bone metabolic response to acidosis (Study 3) and exercise type (Study 4). Additionally, we will examine how important nutritional factors - namely energy availability and protein intake - moderate the bone response to exercise (Study 5). There is a critical need to understand better the specific factors that regulate the bone response to exercise, to ensure that lifestyle intervention interventions and recommendations are effective and fit-for-purpose. Collectively, this ambitious, novel and comprehensive research program will provide unique insights into the complex relationship between exercise and bone, along with the modifiable factors that mediate this response. Importantly, the data attained, in addition to its numerous direct therapeutic and clinical applications, will provide a foundation on which an extensive on-going research program can be built. In line with the objectives of the Young Investigator program, we are confident that the current proposal has all of the ingredients required to develop an innovative and impactful research line and group, that will serve as an internationally recognised centre of excellence for research investigating the bone response to exercise and nutrition, along with the clinical applications of this approach. (AU)

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Scientific publications (11)
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
ESTEVES, GABRIEL P.; MAZZOLANI, BRUNA CARUSO; SMAIRA, FABIANA INFANTE; MENDES, ELIZABETH SILVA; DE OLIVEIRA, GABRIELA GUIMARAES; ROSCHEL, HAMILTON; GUALANO, BRUNO; PEREIRA, ROSA MARIA R.; DOLAN, EIMEAR. Nutritional recommendations for patients undergoing prolonged glucocorticoid therapy. RHEUMATOLOGY ADVANCES IN PRACTICE, v. 6, n. 2, p. 13-pg., . (19/14820-6, 19/05616-6, 16/00006-7, 20/08637-1, 20/07860-9, 19/14819-8)
NICOLETTI, CAROLINA FERREIRA; ESTEVES, GABRIEL PERRI; GENARIO, RAFAEL; SANTO, MARCO AURELIO; DE CLEVA, ROBERTO; GUALANO, BRUNO; ROSCHEL, HAMILTON. Nutritional Inadequacies Among Post-bariatric Patients During COVID-19 Quarantine in Sao Paulo, Brazil. OBESITY SURGERY, v. 31, n. 5, . (20/07860-9, 19/18039-7, 15/26937-4, 17/13552-2)
SMAIRA, FABIANA INFANTE; MAZZOLANI, BRUNA CARUSO; ESTEVES, GABRIEL PERRI; ANDRE, HELOISA C. SANTO; AMARANTE, MILLA CORDEIRO; CASTANHO, DANIELA FERNANDES; CAMPOS, KAREN JENNIFER DE; BENATTI, FABIANA BRAGA; PINTO, ANA JESSICA; ROSCHEL, HAMILTON; et al. Poor Eating Habits and Selected Determinants of Food Choice Were Associated With Ultraprocessed Food Consumption in Brazilian Women During the COVID-19 Pandemic. FRONTIERS IN NUTRITION, v. 8, . (19/14819-8, 20/07860-9, 17/13552-2, 15/26937-4, 19/14820-6)
ESTEVES, GABRIEL P.; MAZZOLANI, BRUNA CARUSO; SMAIRA, FABIANA INFANTE; SANTO ANDRE, HELOISA C.; IRAHA, AMANDA YURI; ASTLEY, CAMILLA; MARQUES, ISABELA GOUVEIA; AMARANTE, MILLA CORDEIRO; REZENDE, NATHALIA SAFFIOTI; SIECZKOWSKA, SOFIA MENDES; et al. Food consumption based on processing level (according to Nova system) during the COVID-19 pandemic among adolescents with immunocompromised conditions: a case-control study. FRONTIERS IN NUTRITION, v. 10, p. 9-pg., . (21/02742-0, 19/14820-6, 17/13552-2, 15/26937-4, 20/07860-9, 15/03756-4, 20/02741-1, 19/20814-9, 16/00006-7, 19/14819-8, 19/15231-4)
MARTICORENA, FELIPE MIGUEL; BARRETO, GABRIEL CASTANHO; GUARDIEIRO, NATALIA MENDES; ESTEVES, GABRIEL PERRI; OLIVEIRA, TAMIRES NUNES; DE OLIVEIRA, LUANA FARIAS; PINTO, ANA LUCIA DE SA; RIANI, LUIZ; PRADO, DANILO MENDES; SAUNDERS, BRYAN; et al. Performing moderate to severe activity is safe and tolerable for healthy youth while wearing a cloth facemask. PLoS One, v. 18, n. 3, p. 11-pg., . (21/05847-8, 16/50438-0, 20/12036-3, 17/13552-2, 20/07860-9, 20/04368-6)
BÁRBARA FERREIRA VERCESI; IZABELA SPERETA MOSCARDINI; GABRIEL PERRI ESTEVES; REBECA ANTUNES BERALDO. Patients living with HIV have quantitatively inadequate food consumption. ARCHIVES OF ENDOCRINOLOGY METABOLISM, v. 67, n. 5, . (20/07860-9, 19/12904-8, 17/00692-0)
ESTEVES, GABRIEL P.; NOVELLI, FABIULA ISOTON; MELETTI, MATHEUS MOLINA; COSTA, LUIZ AUGUSTO RIANI; DO PRADO, DANILO MARCELO LEITE; MOLLER, GABRIELLA BERWIG; MARTICORENA, FELIPE MIGUEL; FRANCO, RUTH ROCHA; COMINATO, LOUISE; DOS SANTOS, CLAUDIA RENATA PINTO; et al. Cloth masks during exercise are safe and tolerable for children with overweight and obesity. PEDIATRIC PULMONOLOGY, v. 58, n. 7, p. 4-pg., . (21/05847-8, 19/18039-7, 17/13552-2, 20/07860-9, 20/15678-6)
MAZZOLANI, BRUNA CARUSO; SMAIRA, FABIANA INFANTE; ESTEVES, GABRIEL PERRI; SANTO ANDRE, HELOISA C.; AMARANTE, MILLA CORDEIRO; CASTANHO, DANIELA; CAMPOS, KAREN; BENATTI, FABIANA BRAGA; PINTO, ANA JESSICA; ROSCHEL, HAMILTON; et al. Influence of Body Mass Index on Eating Habits and Food Choice Determinants Among Brazilian Women During the COVID-19 Pandemic. FRONTIERS IN NUTRITION, v. 8, . (20/07860-9, 17/13552-2, 15/26937-4, 19/14819-8, 19/14820-6)
ESTEVES, GABRIEL P.; SWINTON, PAUL; SALE, CRAIG; GUALANO, BRUNO; ROSCHEL, HAMILTON; DOLAN, EIMEAR. Use of factor analysis to model relationships between bone mass and physical, dietary, and metabolic factors in frail and pre-frail older adults. Journal of Applied Physiology, v. 135, n. 1, p. 8-pg., . (17/13552-2, 19/05616-6, 20/07860-9, 19/26899-6)
ANDRE, HELOISA C. SANTO; ESTEVES, GABRIEL P.; BARRETO, GABRIEL. H. C.; LONGHINI, FERNANDO; DOLAN, EIMEAR; BENATTI, FABIANA B.. The Influence of n-3PUFA Supplementation on Muscle Strength, Mass, and Function: A Systematic Review and Meta-Analysis. ADVANCES IN NUTRITION, v. 14, n. 1, p. 13-pg., . (19/17912-9, 19/05616-6, 20/12036-3, 20/07860-9, 19/26899-6, 20/02741-1, 21/12116-0)
ESTEVES, GABRIEL PERRI; SWINTON, PAUL; SALE, CRAIG; JAMES, RUTH M.; ARTIOLI, GUILHERME GIANNINI; ROSCHEL, HAMILTON; GUALANO, BRUNO; SAUNDERS, BRYAN; DOLAN, EIMEAR. Individual Participant Data Meta-Analysis Provides No Evidence of Intervention Response Variation in Individuals Supplementing With Beta-Alanine. INTERNATIONAL JOURNAL OF SPORT NUTRITION AND EXERCISE METABOLISM, v. 31, n. 4, p. 305-313, . (19/05616-6, 20/07860-9, 19/25032-9, 16/50438-0, 19/26899-6)

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